| Project/Area Number |
10670106
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | NATIONAL CHILDREN'S MEDICAL RESEARCH CENTER |
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Principal Investigator |
TANOUE Akito NATIONAL CHILDREN'S MEDICAL RESEARCH CENTER, ASSOCIATE DIRECTOR, 小児医療研究センター・小児薬理研究部, 室長 (60301800)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIKI Natsuko , 共同研究員
TSUJIMOTO Gozoh NATIONAL CHILDREN'S MEDICAL RES. CENTER, DIRECTOR, 小児医療研究センター・小児薬理研究部, 部長 (80172013)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | α1 adrenergic receptor / gene targeting / knockout mouse / α1アドレナリン受容体 / ノックアウト / キメラマウス / マウス未分化胚細胞 / ヘテロ接合体 / ホモ接合体 |
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| Research Abstract |
α1-ARs play critical roles in the regulation of a variety of physiological processes. Increasing evidence suggests that these physiological responses are regulated by multiple receptor subtypes that are structurally homologous. Molecular cloning identified three distinct cDNA encoding α1-AR subtypes (α1a, α1b, α1d). Among the α1-AR subtypes, the function of the α1D-AR remains uncertain, although it is expressed in various tissues. In order to examine the physiological role and the structure-function relationship, we cloned and characterized a gene for the murine α1D-AR. Using a rat α1D-AR cDNA as a probe, the gene for the murine α1D-AR gene is cloned from murine genomic libraries. It consists of two exons and an intron which is over 5 kilobases and interrupts the coding region of the sixth trasmembrane domain. With these information and DNA fragments, a targeting vector for disrupting the gene in mice was constructed and transfected into ES cells. Several positive clones were isolated which were used for blastocyteinjenction. Homozygous mutant mice for α1D-AR were generated. They look normal and proved to be fertile. These mice should be useful for analysis for interaction among α1-ARs.
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